Histological, histochemical, and immunohistochemical characterization of the gill skeleton in the silver carp (Hypophthalmichthys molitrix).

Fibromatous epulis of periodontal ligament origin (FEPLO), also known as peripheral odontogenic fibroma (POF), is a benign gingival lesion that occurs frequently in dogs. Common use of both names is cumbersome and confusing yet persists due to disagreement regarding pathogenesis. With the objective of clarifying the histogenesis and pathogenesis, 100 canine FEPLO/POF lesions that had been surgically excised en bloc were evaluated histologically to characterize the lesion's relationship to surrounding anatomic structures and to document concurrent pathologies in those tissues. No lesions involved the periodontal ligament space, although 88/100 (88%) lesions attached to alveolar bone, similar to the normal anatomy of the gingival ligament. The lesions consist of fibrous tissue with osteogenic potential, and 54/100 (54%) lesions had bone or cemento-osseous matrix. Odontogenic epithelium was evident in 63/100 (63%) lesions, and the paradental location of the epithelium suggests that the origin of most odontogenic epithelium in FEPLO/POF lesions is a result of hyperplastic junctional epithelium extending into the lesion. Hypercellularity was interpreted as a feature of reactive lesions since 15/17 (88%) hypercellular lesions were ulcerated and 15/17 (88%) were inflamed. Frequent concurrent histologic findings included hypercementosis at the cementoenamel junction of the adjacent tooth (79/89, 89%), reactive alveolar bone (90/100, 90%), and inflammation of alveolar bone (67/100, 67%). While the pathogenesis cannot be determined with absolute certainty, available evidence supports a reactive, hyperplastic process rather than neoplastic. The authors believe that fibromatous hyperplasia of the gingival ligament is an anatomically correct name that accurately reflects the likely etiopathogenesis.

Arthrofibrosis is a common complication following total knee arthroplasty (TKA), characterized by excessive fibrous tissue formation within the joint, leading to restricted range of motion, pain, and functional limitations. This review focuses on three key areas: (1) dysregulated wound healing processes and molecular risk factors; (2) histopathological and immunohistochemical features; and (3) emerging molecular targets and potential personalized treatment strategies. Dysregulated wound healing after TKA leads to persistent fibroblast and myofibroblast activation, excessive extracellular matrix deposition, and joint capsule contracture. Key molecular mediators, such as transforming growth factor-β 1 (TGF-β1), xylosyltransferase-I (XT-I), and β-catenin (β-catenin), drive these processes, exacerbating fibrosis. Genetic predisposition, inflammatory signaling, and immune cell infiltration further contribute to the progression of arthrofibrosis. Histopathologically, arthrofibrotic tissue shows increased collagen types I and III deposition, along with upregulated markers such as α-smooth muscle actin and TGF-β1 receptor 1, reflecting myofibroblast activation and inflammation. Immunohistochemical analysis reveals abundant CD68+ macrophages and T cell infiltration, supporting the inflammatory microenvironment. Recent advances in molecular profiling have identified potential biomarkers and therapeutic targets, including bromodomain-containing protein 4 and XT-I, offering hope for personalized medicine. Despite promising preclinical findings, clinical translation remains in its early stages. Future research should prioritize the validation of these biomarkers and explore genetic and epigenetic stratification to improve management and outcomes for high-risk patients.

Chronic expanding hematoma (CEH) is a rare, indolent entity mostly linked to prior tuberculosis, thoracic surgery or trauma, with gradual long-term enlargement and potentially fatal complications. We present a 73-year-old Nepalese male without classic predisposing risk factors, presenting with mild hemoptysis in 2017 and a large right pleural hematoma on computed tomography (CT). He declined surgical evacuation and later developed progressive hematoma expansion and subsequent life-threatening hemoptysis complicated by type 2 respiratory failure and suspected bronchopleural fistula in 2025. He was deemed inoperable, failed conservative management and succumbed to nosocomial pneumonia. Post-mortem histology confirmed CEH with dense fibrous tissue and organized blood clot. This case highlights early recognition and surgical intervention as critical for CEH, even in patients without antecedent thoracic insult.

Arthrofibrosis is a common complication following total knee arthroplasty (TKA), characterized by excessive fibrous tissue formation within the joint, leading to restricted range of motion (ROM), pain, and functional impairment. Accurate diagnosis is essential for distinguishing arthrofibrosis from other causes of postoperative knee stiffness, such as infection, mechanical block, or malalignment. This review aims to explore current diagnostic methods and evolving standards for arthrofibrosis after TKA, focusing on (1) clinical differentiation from other causes of knee stiffness; (2) assessment and diagnostic criteria; (3) imaging, laboratory, and histopathological techniques; and (4) an integrated diagnostic algorithm and future directions. Diagnosis is primarily based on persistent ROM limitation (flexion <90 degrees or extension >5 degrees) for more than 12 weeks, after excluding infection and mechanical causes. Advanced magnetic resonance imaging (MRI) with metal artifact reduction techniques can be used to visualize intra-articular fibrosis, with an MRI-based synovial classification correlating with ROM deficits and severity. Synovial fluid analysis helps rule out infection, and histopathology is employed when the diagnosis remains unclear. The study proposes a stepwise diagnostic algorithm that integrates clinical, imaging, and laboratory findings and discusses future directions for optimizing diagnosis and treatment pathways to improve patient outcomes.

In the August 2025 issue, I read with great interest the article reassessing the histologic validity of the onychodermis in both adult and polydactyly nail units.1 Although Perrin questioned the existence of the onychodermis and onychofibroblasts, our recent histologic, immunohistochemical, and molecular studies in both polydactyly and adult nail units provide compelling evidence supporting their presence.2–4 First, contrary to his suggestion that this concept represents an oversimplification, the recognition of the onychodermis and its resident onychofibroblasts is fundamental to nail biology. These structures play critical roles in nail formation and growth through the epithelial–mesenchymal interactions, and in the pathogenesis of nail tumors such as onychomatricoma.2–9 The onychodermis is a specialized mesenchymal region beneath the nail matrix and nail bed (Fig. 1), distinct from ordinary dermis in both structure and function. The onychodermis can be distinguished from the surrounding skin dermis, which contains conventional dermal fibroblasts and adnexal structures. The nail matrix onychodermis is composed of an upper dense collagenous layer and an underlying, less eosinophilic, loosely cellular zone known as the onychomatricodermis. The nail matrix onychodermis contributes to nail plate formation by interacting with the nail matrix. In contrast, the nail bed onychodermis appears as a dense collagenous layer including thick fibrous tissue that anchors the nail bed to the distal phalanx, primarily contributing to the mechanical support for the nail plate. Despite these histologic differences, both regions share common features in histology, immunohistochemistry, and gene expression. These similarities support the concept of the onychodermis as a distinct nail-specific mesenchymal tissue. RSPO4 is a key nail-specific gene involved in nail development, and mutations in RSPO4 are associated with anonychia.10 This gene is expressed in onychofibroblasts within the onychodermis of the nail matrix and nail bed. In addition, our recent spatial transcriptomic profiling demonstrated that both the onychodermis and the follicular dermal papilla expressed Wnt- and BMP-related signaling molecules, suggesting that the onychodermis serves as the nail unit's counterpart to the dermal papilla of hair follicles.4FIGURE 1.: Simplified illustration of the onychodermis in the human nail unit. Blue area shows Onychodermis.Second, Perrin repeatedly referred to the lower portion of the nail matrix onychodermis as the “matrix hypodermis.” However, this terminology is anatomically incorrect because this region belongs to the onychodermis rather than to the subcutaneous hypodermis although age-related fatty changes may be observed in the deeper portion of the nail matrix onychodermis in adult nail units. RSPO4 is expressed in onychofibroblasts within the nail matrix onychodermis, including the region he referred to as the “matrix hypodermis.” Third, he recently proposed the presence of so-called telocytes in the nail unit; however, both the terminology and the described cellular characteristics closely resemble those of previously described and extensively characterized onychofibroblasts. In conclusion, recognition of the onychodermis and its resident onychofibroblasts is essential for advancing our understanding of nail biology and pathology.

In soft tissue pathology, MUC4 is considered a sensitive and specific immunohistochemical marker for low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF), which are characterized by FUS/EWSR1 :: CREB3L2/1 fusions. Recently, MUC4-positive fibroblastoma has been proposed as a novel entity, and we herein describe 7 cases that align with this disease concept. These tumors occurred in 7 female patients aged 14 to 60 years, and they were located in the neck (2 cases), temple, arm, chest wall, pharynx, and thigh, with 5 being deep-seated. All tumors were surgically removed. No patients experienced recurrence during follow-up periods of 2 to 113 months. The well-circumscribed tumors comprised hypocellular fibrous tissue, populated by nonatypical spindle cells. Myxoid stroma was absent. Common features included thin-walled patent vessels, extremely long vessels, and mast cells. In some cases, fat entrapment/overgrowth was conspicuous. All tumors tested positive for MUC4 and nuclear β-catenin expression. The tumors were molecularly investigated with fluorescence in situ hybridization, RNA sequencing, DNA panel sequencing, DNA methylation analysis, and/or nanopore sequencing. Genetic analysis showed the absence of FUS/EWSR1 fusions in all 7 cases. All 5 tested tumors harbored APC alterations, with 3 having inactivating mutations and 2 showing copy number loss. DNA methylation profiles of 2 tumors did not match those of any references, including LGFMS or SEF, as indicated by t-SNE. Overall, our study supports the recent proposal of MUC4-positive fibroblastoma as a distinct entity and further delineates its phenotypic and molecular characteristics. These tumors should be distinguished from LGFMS, SEF, desmoid fibromatosis, and other fibrous or fibroadipose tumors.

Enlarged parietal foramina (EPF) are rare, bilateral, symmetric calvarial defects, most commonly inherited in an autosomal-dominant manner. We report an exceptionally rare case of a ruptured parietal arteriovenous malformation (AVM) situated immediately beneath an EPF and resected via the calvarial defect. A 46-year-old man with no prior medical history presented with acute left upper-limb incoordination. Head computed tomography revealed a 3-cm right parietal subcortical hemorrhage and bilateral symmetric parietal defects; similar defects in his mother, uncle, and grandfather supported a diagnosis of familial EPF. The hemorrhage was directly subjacent to the defect, without antecedent trauma. Angiography identified a Spetzler-Martin grade I AVM within the hematoma. Using the EPF as a corridor, microsurgical resection was performed. The osseous defect was filled with fibrous connective tissue, and the dura was focally thickened with firm dural-arachnoid adhesions. The AVM nidus was removed en bloc. Postoperatively, left upper-limb incoordination resolved promptly and the patient was discharged with a modified Rankin Scale score of 0. Histopathology confirmed an AVM nidus and demonstrated infiltration of inflammatory cells, including polymorphonuclear leukocytes, around abnormal vascular walls and within the dura. Whole-genome sequencing revealed a pathogenic ALX4 nonsense variant (c.793C>T, p.Arg265Ter) and no pathogenic variants in established brain-AVM predisposition genes. The spatial concordance of EPF and AVM, together with the inflammatory histopathology, raises the possibility that EPF-associated inflammation may influence subjacent AVM biology or rupture susceptibility, although causality remains unproven.

Serial OCT-based coronary physiology and plaque composition in vessels with nonobstructive coronary lesions following intensive lipid-lowering therapy: YELLOW III sub-study.

An 87‐year‐old man underwent transcatheter edge‐to‐edge repair (TEER), one MitraClip NT︎ from anterior commissure (AC), 8 months prior for severe mitral regurgitation (MR) due to functional etiology and A1 chordal rupture, complicated by heart failure. Following improvement in heart failure, he was discharged home independently 2 weeks postprocedure. However, 4 months ago, he experienced worsening heart failure, and echocardiography revealed recurrent severe MR due to single leaflet device attachment (SLDA) at P1, prompting a surgical intervention. Intraoperatively, after establishing cardiopulmonary bypass and inducing cardiac arrest, transseptal access revealed the MitraClip NT︎ firmly adhered to the P1 leaflet and extensive rupture of the A1 chordae. The MitraClip NT︎ and involved leaflet tissue were excised en bloc, the defect was repaired, artificial chordae were implanted, edge‐to‐edge repair of the AC region was performed, and a prosthetic annuloplasty ring was sutured in place, successfully eliminating regurgitation. Since MitraClip NT︎ becomes encapsulated by fibrous tissue within 2–3 months postimplantation, isolated removal becomes technically difficult in the late phase. Therefore, en bloc resection with the leaflet is necessary in cases of SLDA‐related recurrent MR. SLDA involving the posterior mitral leaflet is considered more amenable to mitral valve repair than that involving the anterior mitral leaflet. Patients selected for TEER generally have limited surgical tolerance; thus, minimizing operative and cardiopulmonary bypass times is essential. Surgical approach should be tailored based on leaflet morphology and clip location.

Deep brain stimulation (DBS) has been shown to provide benefits for dystonia beyond 15 years. However, the long-term biological response to chronically implanted DBS hardware and its structural integrity over such extended periods remain poorly characterized. Pathological examination of explanted leads and especially those implanted for over a decade or more has been rarely performed. The aim was to document the pathological findings of bilaterally explanted globus pallidus pars interna (GPi) DBS leads after 15 years of continuous therapy in a patient with DYT-1 dystonia. We present the case of a 23-year-old woman with genetically confirmed DYT-1 dystonia who underwent bilateral GPi DBS implantation at the age of 8. After 15 years of stable therapeutic benefit, she experienced progressive functional decline despite extensive reprogramming attempts. Bilateral lead revision was performed, and the explanted DBS leads were examined macroscopically and microscopically. The explanted leads demonstrated striking macroscopic abnormalities, including membrane coating and mild contact degradation. Microscopic examination revealed extensive fibrous tissue encapsulation and adherent coagulated brain tissue, suggestive of a mild chronic foreign body response. The left DBS lead revealed a decreased electrical impedance, and this was correlated with contact degradation. Despite lead revision, no definitive symptom improvement occurred after 9 months. These findings suggest that DBS leads may maintain therapeutic function despite significant biological and structural changes over a 15-year period. Hardware integrity in this case did not correlate with clinical effectiveness.

An intramural course in an anomalous aortic origin of a coronary artery (AAOCA) is a high-risk feature for sudden cardiac death (SCD). One of the proposed mechanisms for this association involves a "flap valve" effect in the intramural segment. The (patho-)histological characteristics of this segment may contribute to risk stratification, however, current data are scarce. The aim of this study was to identify the histological features of the intramural segment and their potential relevance to vascular wall properties and the aortic valve commissure, thereby providing insights into possible functional implications of AAOCA. This prospective multicenter study included consecutive pediatric and adult AAOCA patients who underwent surgical unroofing between 2021 and 2024. The excised arterial vascular wall tissue (i.e. the intramural segment), was immunohistochemically examined for vascular wall components. Two independent observers reviewed the data, correlating findings with preoperative CTA to assess spatial relationships with surrounding aortic and AAOCA tissues. Results were also compared with a post-mortem AAOCA specimen and control tissues. Fifteen patients (mean age 42.9 ± 14.0 years, age range 11-66 years, 60% female) undergoing surgery for AAOCA were included. Fourteen patients (93%) had an anomalous aortic origin of a right coronary artery (AAORCA) and one patient (7%) had an anomalous aortic origin of a left coronary artery (AAOLCA). The mean intramural segment length was 7.8 ± 3.6mm in AAORCA and 16.0mm in the AAOLCA. Histologically, a two-layered tunica media without interposing tunica adventitia was identified in all intramural segments. Pre-operative CTA showed a close spatial relationship of the aortic side of the intramural segment with the aortic valve commissure. In line with this, extensive fibrous tissue was observed histologically on the aortic side of the intramural segment, consistent with commissure. In contrast, the vascular wall on the coronary arterial side of the intramural segment showed overall medial degeneration, characterized by mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, elastic fiber thinning, loss of smooth muscle cell nuclei, and collagen alterations. These abnormalities were more prevalent with increasing age. Histology of the intramural segment revealed structural alterations which may be consistent with reduced vascular compliance. Further studies, including post-SCD specimens, are needed to refine risk stratification.

Intermediate filaments (IF) are diverse and cell-type specific. The IF protein vimentin, expressed in mesenchymal cells and different cancer cells, is functionally associated with cell migration through fibrous tissues. Vimentin increases cell elongation needed for migration, yet also acts as a cytoskeletal cage that hinders cells squeezing through small spaces. To determine how vimentin facilitates cell migration through the extracellular matrix (ECM) and around neighboring cells in tissues, we examine the collective invasion of cell spheroids embedded in collagen networks. Unlike single-cell migration in collagen networks, the collective invasion of cells through the collagen network is increased by vimentin for both mouse embryonic fibroblasts (MEF) and co-cultures of MEF with MDA-MB-231 breast cancer cells. Using multiple experimental systems, we show that vimentin increases spheroid contractility and that vimentin-mediated collective cell expansion depends on matrix metalloproteinases (MMP), which degrade collagen networks. In addition, through advanced imaging and a computational 3D cell vertex model, we find that vimentin enhances the elongation of cells in spheroids embedded in collagen, indicating increased spheroid fluidity and active collagen contraction. Altogether, these results reveal new insights on vimentin's effects in enhancing collective cell migration in 3D matrix environments through collagen remodeling and tissue fluidity.

The umbilicus is a distinct anatomical feature of the anterior abdominal wall, characterized by persistent postnatal depression. Despite its clinical and surgical relevance, the histological and spatial structures underlying the umbilical concavity remain unclear. Herein, we investigated the fibrous connective tissue underlying the umbilical concavity.Five formalin-fixed cadaveric specimens (mean age: 77.4 years) were used. Two were used for macroscopic dissection, two for histological examination, and one for quasi-continuous serial sectioning with three-dimensional reconstruction.Macroscopic dissection revealed a vertically cylindrical fibrous structure extending from the umbilical fossa to the anterior rectus sheath. Histological analysis confirmed that this structure enclosed a small fat compartment distinct from subcutaneous fat, representing an extraperitoneal fat protrusion in contact with the underside of the umbilical skin. Serial sections and three-dimensional reconstruction identified a tunnel-like fibrous structure, termed "umbilical sheath," enveloping the protruded fat and bridging the umbilical ring and dermis. This sheath connected the invaginated skin to the linea alba and rectus sheath.We identified a previously undescribed fibrous structure, the umbilical sheath, enclosing a localized protrusion of extraperitoneal fat, maintaining umbilical concavity. Recognition of this structure may guide optimal port placement and promote abdominal wall closure techniques that preserve anatomical support, potentially reducing incisional hernia risk.

Computational modelling of the electrical fields generated by helical electrodes surrounding the vagus nerve suggested a current of 1.0mA should depolarise enough axons to give a therapeutic effect in epilepsy. An assumption that fibrous tissue formation would form between the electrodes and the nerve in implantable vagus nerve stimulators (VNS) led to the recommendation that 1.5mA should be used to account for the increased impedance this would cause. This increase in impedance has not been documented, meaning that the higher current might not be necessary and could produce avoidable adverse effects such as coughing. To test the hypotheses that impedance does not always increase following VNS implantation and that more adverse effects might be seen with lower impedance circuits, circuit impedance was measured in dogs with implantable VNS at implantation and compared to impedance at 3-6 months post-implantation and at non-standardised time points thereafter. Dogs were grouped by severity of their coughing and the impedance between groups at 3-6 months was compared. Mean impedance at first implantation (2219Ω, 95% CI 1894-2544) was no different from impedance at 3-6 months post implantation (2257Ω, 95%CI 1944-2570, p = .80). Only 2 of 17 dogs showed a > 50% increase in impedance (one at 3-6 and one at 7-12 months). Coughing severity was not influenced by impedance value despite similar stimulation currents. This work shows impedance does not consistently increase post implantation in dogs with VNS, suggesting that currents > 1.0mA might not be routinely needed to achieve a therapeutic effect.

Fibrosing mediastinitis (FM) is a rare chronic fibrotic disease of the mediastinum, characterized by diffuse fibrous tissue proliferation in the mediastinal space that can compress adjacent pulmonary vessels bilaterally. This fibrous proliferation is the core pathological basis for simultaneous stenosis of pulmonary arteries (PAs) and pulmonary veins (PVs) in affected patients, with adhesion as a secondary pathological manifestation of FM rather than the primary cause of vascular stenosis. Fibrous tissue proliferation compresses the pulmonary veins, causing stenosis, obstructing pulmonary circulation reflux, leading to pulmonary congestion and pulmonary hypertension, with symptoms such as dyspnea and hemoptysis. Diagnosis relies on contrast-enhanced chest CT and pulmonary angiography, and multimodal endovascular imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can provide refined morphological details of stenotic lesions. IVUS and OCT revealed a rare triangle-like lumen in FM-induced PV stenosis, a specific imaging feature that supplements the morphological data of FM-related PV stenosis and provides a new intravascular evaluation reference for such rare lesions. The combined use of IVUS and OCT helps differentiate extrinsic compression from intrinsic vascular pathology, which is critical for treatment selection. Treatment is mainly based on drugs to inhibit fibrosis, interventional procedures or surgery to relieve obstruction. This case suggests that a triangle-like lumen on intravascular imaging may represent a useful clue to FM-induced pulmonary vein stenosis. However, this is a single observation; the specificity of the triangle-like lumen for FM remains unknown. Combined IVUS and OCT is resource-intensive and not routinely recommended. We report this morphology solely as a potential diagnostic clue when clinical suspicion of FM exists.

Tunneled-cuffed catheters (TCCs) remain a primary vascular access modality for patients requiring maintenance hemodialysis, yet catheter dysfunction is a frequent and challenging complication. Although the factors contributing to catheter dysfunction are well recognized, the ultrastructural changes of fibrin sheaths in long-term indwelling catheters have not been systematically documented in the literature. Herein, we present 4 cases of malfunctioning subcutaneous TCCs of varying dwelling durations. Catheter exchange was performed under digital subtraction angiography guidance, and fibrin sheath specimens were collected for analysis. Ultrastructural assessment was conducted via scanning electron microscopy, supplemented with energy-dispersive X-ray spectroscopy and hematoxylin-eosin staining. Fibrous tissue hyperplasia was observed in all 4 specimens. Specimens from the 2 catheters with longer dwelling durations exhibited myofiber degeneration within the fibrin sheaths, accompanied by tissue calcification. In contrast, fibrin sheaths from the 2 catheters with shorter dwelling durations were predominantly characterized by exudates and inflammatory cellular infiltration. Fibrin sheath hyperplasia is a consistent pathological feature in long-term hemodialysis catheters. These findings suggest that prolonged catheter dwelling time correlates with progressively more severe pathological changes in the fibrin sheath.

Background and Objectives: Breast cancer remains one of the most common malignancies worldwide, and early detection plays a crucial role in improving treatment outcomes and reducing mortality. Several experimental studies using animal models of breast cancer have explored the potential of terahertz-based technologies in this field. However, their preclinical evidence base in breast cancer remains heterogeneous and has not been systematically synthesized with a focus on experimental models, imaging protocols, and barriers to translation. Methods: We conducted a descriptive systematic review, according to PRISMA guidelines, of 10 articles selected from a total of 372 identified across four databases-PubMed, Embase, Web of Science, and Cochrane-regarding the diagnostic performance of terahertz (THz) imaging in breast cancer animal models. We included studies that used rodent models diagnosed with breast cancer, subsequently confirmed through histological examination, and extracted relevant data. Results: The results were synthesized using a narrative approach. Most studies used C57BL/6J mice with E0771 cell line-induced breast tumors, with histopathology as the reference standard. In the reflection mode, at frequencies between 0.1 and 4 THz, the identification of tumoral, fibrous, fat, and muscle tissues was possible. Conclusions: Overall, the available preclinical evidence supports THz imaging as a promising proof-of-concept approach for breast tissue characterization, but not yet as a standardized or clinically translatable diagnostic platform. Future studies should use harmonized animal models, standardized acquisition and specimen-handling protocols, transparent reporting of classification workflows, and consistent outcome metrics to enable comparison across studies and to clarify the biological and biophysical determinants of THz contrast in breast cancer.

ABSTRACTFibromas of the oral cavity are benign proliferations of fibrous connective tissue, most commonly occurring in areas subject to chronic trauma, such as the buccal mucosa, tongue, and lips. Fibromas of the hard palate, particularly those of large size, are extremely rare. A 61‐year‐old female presented with a slow‐growing, painless lesion on the midline of the hard palate that caused discomfort during mastication. Clinical examination revealed a firm, pedunculated, pale pink, cauliflower‐like lesion measuring 2.5 × 3.6 cm. CT imaging showed no underlying bone involvement. An excisional biopsy was performed under local anesthesia, and hemostasis was achieved using ferric sulfate gel. Histopathological examination confirmed the diagnosis of fibroma. Postoperative healing was uneventful, with minimal discoloration at the surgical site. This case highlights the rare presentation of a large palatal fibroma, underscores the importance of considering uncommon sites in diagnosis, and demonstrates the safe use of ferric sulfate gel for intraoperative hemostasis.

Intracranial aneurysm (IA) is a leading cause of subarachnoid hemorrhage, characterized by complex pathogenesis and high mortality rates due to rupture. The aim of this study was to develop a targeted glucagon-like peptide-1 (GLP-1) nanodelivery system to mobilize endothelial progenitor cells (EPCs) and enhance re-endothelialization in a rat model of coiled IA. In this study, a matrix metalloproteinase-2 (MMP-2)-targeted nanodelivery platform (hereafter GLP-1@tMSN [targeted mesoporous silica nanoparticle]) based on MSNs functionalized with GLP-1 was developed to mobilize EPCs and accelerate vascular repair. The efficacy of GLP-1@tMSN in promoting EPC recruitment and re-endothelialization was evaluated in a rat coiled aneurysm model, alongside mechanistic studies of the Wnt/β-catenin signaling pathway. In a rat model of coiled IA, GLP-1@tMSN significantly enhanced the recruitment of EPCs and promoted re-endothelialization. Histological analysis demonstrated the formation of mature endothelial-like tissue after 28 days, in contrast to the fibrous tissue observed in the control group. Immunofluorescence analysis confirmed the preferential accumulation of CD34+VEGFR2+ EPCs at the lesion site, with concurrent activation of the Wnt/β-catenin pathway, implicating its pivotal role in driving vascular repair. Preliminary safety evaluations further indicated a favorable biocompatibility profile for the nanotherapeutic system. The developed functionalized nanodelivery platform represents a promising therapeutic strategy to enhance localized GLP-1 efficacy, facilitating rapid re-endothelialization and potentially reducing long-term recurrence of IAs after embolization. This approach shows substantial potential for improving outcomes for patients with IA.